Association between various physical factors and acute thoracolumbar intervertebral disk extrusion or protrusion in Dachshunds.

OBJECTIVE To determine whether body weight, body condition score, or various body dimensions were associated with acute thoracolumbar intervertebral disk extrusion or protrusion and whether any of these factors were associated with severity of clinical signs in Dachshunds. DESIGN Cross-sectional clinical study. ANIMALS 75 Dachshunds with (n = 39) or without (36) acute thoracolumbar intervertebral disk extrusion or protrusion. PROCEDURES Signalment, various body measurements, body weight, body condition score, and spinal cord injury grade were recorded at the time of initial examination. RESULTS Mean T1-S1 distance and median tuber calcaneus-to-patellar tendon (TC-PT) distance were significantly shorter in affected than in unaffected dogs. A 1-cm decrease in T1-S1 distance was associated with a 2.1-times greater odds of being affected, and a 1-cm decrease in TC-PT distance was associated with an 11.1-times greater odds of being affected. Results of multivariable logistic regression also indicated that affected dogs were taller at the withers and had a larger pelvic circumference than unaffected dogs, after adjusting for other body measurements. Results of ordinal logistic regression indicated that longer T1-S1 distance, taller height at the withers, and smaller pelvic circumference were associated with more severe spinal cord injury. CONCLUSIONS AND CLINICAL RELEVANCE Results suggest that certain body dimensions may be associated with acute thoracolumbar intervertebral disk extrusion or protrusion in Dachshunds and, in affected dogs, with severity of neurologic dysfunction.

Pollen and charcoal in lake sediments compared with historically documented forest fires in southern Switzerland since AD 1920

Charcoal in unlaminated sediments dated by 210Pb was analysed by the pollen-slide and thin-section methods. The results were compared with the number and area of forest fires on different spatial scales in the area around Lago di Origlio as listed in the wildfire database of southern Switzerland since AD 1920. The influx of the number of charcoal particles > 75 µm2 in pollen slides correlates well with the number of annual forest fires recorded within a distance of 20-50 km from the coring site. Hence a size-class distinction or an area measurement by image analysis may not be absolutely necessary for the reconstruction of regional fire history. A regression equation was computed and tested against an independent data set. Its use makes it possible to estimate the charcoal area influx (or concentration) from the particle number influx (or concentration). Local fires within a radius of 2 km around the coring site correlate well with the area influx of charcoal particles estimated by the thin-section method measuring the area of charcoal particles larger than 20 000 µm2 or longer than 50 µm. Pollen percentages and influx values suggest that intensive agriculture and Castanea sativa cultivation were reduced 30-40 years ago, followed by an increase of forest area and a development to more natural woodlands. The traditional Castanea sativa cultivation was characterized by a complete use of the biomass produced, so abandonment of chestnut led to an increasing accumulation of dead biomass, thereby raising the fire risk. On the other hand, the pollen record of the regional vegetation does not show any clear response to the increase of fire frequency during the last three decades in this area.

Signal transduction of CEACAM1-L tumor suppressor

CEACAM1-L is an adhesion molecule that suppress the growth of prostate, breast, colon and endometrial tumors. In this study we defined the domain involved in CEACAM1-L tumor suppression activity. DU145 prostate cancer cells were infected with recombinant adenoviruses containing various CEACAM1-L mutant genes, and the effects of the mutant proteins on the growth of DU145 cells were assessed in a nude-mice xenograft model. We found that expression of the CEACAM1-L cytoplasm domain alone led to growth suppression of DU145 cells. These results suggest that the cytoplasmic domain of CEACAM1-L is necessary and sufficient for its growth-suppressive function. ^ The cytoplasmic domain of CEACAM1-L is presumed to be involved in a signaling pathway resulting in the suppression of tumor cell growth. It was not clear whether post-translational modification of CEACAM1-L is required for tumor suppressor function, therefore the importance of phosphorylation in growth-inhibitory signaling pathway was investigated. Full-length CEACAM1-L was found to be phosphorylated in vivo in both tyrosine and serine residues. Mutation of tyrosine 488 to phenylalanine did not abolish the tumor-suppressive activity of CEACAM1-L while mutation of serine 503 to alanine abolished the growth-inhibitory activity. In addition, mutation of serine 503 to aspartic acid produced tumor-suppressive activity similar to that of the wild-type CEACAM1-L. These results suggested that only phosphorylation at serine 503 is essential for CEACAM1-L's growth-inhibitory function in vivo. ^ Phosphorylation of CEACAM1-L may lead to its interaction with molecules in CEACAM1-L's signaling pathway. In the last part of this study we demonstrate that CEACAM1 is able to interact with the adapter protein p66Shc. p66Shc was found to be co-immunoprecipitated with full length CEACAM1-L but not with CEACAM1-L lacking its cytoplasmic tail. Additionally this interaction occurred in the absence of the tyrosine phosphorylation of CEACAM1-L. These results suggest that p66Shc is able to interact with the cytoplasmic domain of CEACAM1-L and this interaction does not require tyrosine phosphorylation. ^ In conclusion, this study suggests that CEACAM1-L signals tumor suppression through its cytoplasmic domain by initially becoming phosphorylated on serine 503. Additionally, the interaction with p66Shc may be involved in CEACAM1-L's signaling pathway. ^

Cleavage and activation of calpain and its substrate caspase-7 in prostate cancer cells: Evidence for a role in apoptotic sensitization

Changes in the levels of intracellular calcium mediate multiple biological effects, including apoptosis, in some tumor cells. Early studies demonstrated that prostate cancer cells are highly sensitive to alterations in the levels of their intracellular calcium pools. Furthermore, it has been established that apoptosis in prostate cancer could be initiated through calcium-selective ionophores, or inhibitors of intracellular calcium pumps. High sensitivity to changes in intracellular calcium levels may therefore be exploited as a novel mechanism for controlling prostate cancer apoptotic thresholds; however, the mechanisms associated with this process are poorly understood. To investigate the role of calcium as a mediator of prostate cancer cell death and its effects on caspase activation, LNCaP and PC-3 cell response to the calcium ionophore A23187, were examined. LNCaP cells were highly sensitive to changes in intracellular calcium, and subtoxic concentrations of A23187 facilitated apoptosis initiated by cytokines (TNF or TRAIL). In contrast, PC-3 cell death was not affected by A23187 or cytokines. A23187 caused rapid and concentration-dependent activation of calpain in LNCaP (but not PC-3 cells) which correlated with cleavage of calpain substrates caspase-7 and PTP1B. Cleavage of PTP1B from a 50 kDa to 42 kDa protein correlated with its translocation from the endoplasmic reticulum to the cytosol and with inhibition of tyrosine phosphorylation. Caspase-7 was cleaved from a 35 kDa to 30 kDa protein in response to A23187 in LNCaP (but not PC-3) cells and correlated with activation of both upstream and downstream caspases. Extracts from A23187-treated LNCaP cells, or PC-3 cells transiently transfected with calpain, mediated similar processing of in vitro transcribed and translated (TNT) caspase-7. In vitro processing of caspase-7 correlated with its proteolytic activation, which was inhibited by calpain inhibitor (calpeptin) and to some degree, by caspase inhibitors (zVAD, DEVD). Together, these results suggest that calpain is directly involved in calcium-mediated apoptosis of prostate cancer cells through activation and cleavage of caspase-7 and other substrates. Loss of calpain activation may therefore play a critical role in apoptotic resistance of some prostate cancer cells. ^

Na 1 Nachlass Max Horkheimer, 600 - Korrespondenzen u.a. mit Friedrich Pollock (p. VI 42, 211-386)

Briefwechsel zwischen Max Horkheimer, Frederick Pollock und Karl August und Olga Wittfogel; 2 Briefe zwischen Edith B. Bernett und Max Horkheimer, April 1940; 2 Briefe zwischen Max Horkheimer und Philip Vaudrin, Juli 1939; 3 Briefe an David H. Stevens von Max Horkheimer, 26.03.1938; 1 Brief von A. Radcliffe an Frederick Pollock, 18.11.1937; 3 Briefe an Max Horkheimer von der Columbia University Faculty of Political Science (New York), November 1937; 2 Briefe von der Columbia University Department of History (New York) an Max Horkheimer, November 1937; 1 Brief an Max Horkheimer von Sharon Beard, 27.11.1937; 1 Brief von Ruth Benedict an Max Horkheimer, 19.11.1937; 1 Brief an Max Horkheimer von Franz Boas, 19.11.1937; 1 Brief von R. E. Chaddock an Max Horkheimer, 21.11.1937; 1 Brief an Max Horkheimer von Ch'ao-ting Chi, 19.11.1937; 1 Brief von J. M. Clark an Max Horkheimer, 22.11.1937; 1 Brief an Dr. Wertheimer von Morris R. Cohen, 29.11.1937; 1 Brief von Alfred E. Cohn an Max Horkheimer, 26.11.1937; 1 Brief an Max Horkheimer von John J. Coss, 22.11.1937; 1 Brief von George S. Counts an Max Horkheimer, 24.11.1937; 1 Brief an Max Horkheimer von A. P. Evans, 22.11.1937; 3 Briefe von Gertrude Stewart an Max Horkheimer, 20. - 24.11.1937; 1 Brief an Max Horkheimer von L. C. Goodrich, 22.11.1937; 1 Brief von John W. Innes an Max Horkheimer, 20.11.1937; 1 Brief an Max Horkheimer von Philip C. Jessup, 24.11.1937; 1 Brief von John A. Krout an Max Horkheimer, 23.11.1937; 1 Brief an Max Horkheimer von Bruno Lasker, 20.11.1937; 1 Brief von Samuel McCune Lindsay an Max Horkheimer, 24.11.1937; 1 Brief an Max Horkheimer von K. N. Llewellyn, 26.11.1937; 1 Brief von R. S. Lynd an Max Horkheimer, [November 1937]; 1 Brief an Max Horkheimer von R. M. MacIver, 19.11.1937; 1 Brief von Julian W. Mack an Max Horkheimer, 24.11.1937; 1 Brief an Max Horkheimer von Arthur Maxmahon, 20.11.1937; 1 Brief von Jerome Michael an Max Horkheimer, 26.11.1937; 1 Brief an Max Horkheimer von Wesley C. Mitchell, 22.11.1937; 1 Brief von der Columbia University School of Business (New York) an Max Horkheimer, 22.11.1937; 2 Briefe zwischen Max Horkheimer und der John Simon Guggenheim Memorial Foundation (New York), November 1937; 2 Briefe von der Columbia University Department of Psychology (New York) an Max Horkheimer, November 1937; 1 Brief an Max Horkheimer von Goodwin Watson, 23.11.1937; 1 Brief von Otto Nathan an Max Horkheimer, 26.11.937; 1 Brief an Max Horkheimer von John K. Norton, 23.11.1937; 1 Brief von der Columbia University Department of Chinese (New York) an Max Horkheimer, 23.11.1937; 1 Brief an Max Horkheimer von Gerold Tanquary Robinson, 19.11.1937; 1 Brief von der Columbia University Department of Public Law and Government (New York) an Max Horkheimer, 22.11.1937; 1 Brief an Max Horkheimer von R. C. Sailer, 20.11.1937; 1 Brief von Herbert W. Schneider an Max Horkheimer, 22.11.1937; 1 Brief an Max Horkheimer von R. L. Schuyler, 20.11.1937; 1 Brief von Pauline Steorns an Max Horkheimer, 22.11.1937; 1 Brief an Max Horkheimer von Frank Tannenbaum, 19.11.1937; 1 Brief von Alfred Vagés an Max Horkheimer, 26.11.1937;

Non B-DNA structures and genomic instability associated with myotonic dystrophy type 2 (CCTG).(CAGG) repeats

There are many diseases associated with the expansion of DNA repeats in humans. Myotonic dystrophy type 2 is one of such diseases, characterized by expansions of a (CCTG)•(CAGG) repeat tract in intron 1 of zinc finger protein 9 (ZNF9) in chromosome 3q21.3. The DM2 repeat tract contains a flanking region 5' to the tract that consists of a polymorphic repetitive sequence (TG)14-25(TCTG)4-11(CCTG) n. The (CCTG)•(CAGG) repeat is typically 11-26 repeats in persons without the disease, but can expand up to 11,000 repeats in affected individuals, which is the largest expansion seen in DNA repeat diseases to date. This DNA tract remains one of the least characterized disease-associated DNA repeats, and mechanisms causing the repeat expansion in humans have yet to be elucidated. Alternative, non B-DNA structures formed by the expanded repeats are typical in DNA repeat expansion diseases. These sequences may promote instability of the repeat tracts. I determined that slipped strand structure formation occurs for (CCTG)•(CAGG) repeats at a length of 42 or more. In addition, Z-DNA structure forms in the flanking human sequence adjacent to the (CCTG)•(CAGG) repeat tract. I have also performed genetic assays in E. coli cells and results indicate that the (CCTG)•(CAGG) repeats are more similar to the highly unstable (CTG)•(CAG) repeat tracts seen in Huntington's disease and myotonic dystrophy type 1, than to those of the more stable (ATTCT)•(AGAAT) repeat tracts of spinocerebellar ataxia type 10. This instability, however, is RecA-independent in the (CCTG)•(CAGG) and (ATTCT)•(AGAAT) repeats, whereas the instability is RecA-dependent in the (CTG)•(CAG) repeats. Structural studies of the (CCTG)•(CAGG) repeat tract and the flanking sequence, as well as genetic selection assays may reveal the mechanisms responsible for the repeat instability in E. coli, and this may lead to a better understanding of the mechanisms contributing to the human disease state. ^

Association between glycemic index and glycemic load and the risk of incident coronary heart disease among whites and African Americans with and without type 2 diabetes: The Atherosclerosis Risk in Communities study

Several studies have examined the association between high glycemic index (GI) and glycemic load (GL) diets and the risk for coronary heart disease (CHD). However, most of these studies were conducted primarily on white populations. The primary aim of this study was to examine whether high GI and GL diets are associated with increased risk for developing CHD in whites and African Americans, non-diabetics and diabetics, and within stratifications of body mass index (BMI) and hypertension (HTN). Baseline and 17-year follow-up data from ARIC (Atherosclerosis Risk in Communities) study was used. The study population (13,051) consisted of 74% whites, 26% African Americans, 89% non-diabetics, 11% diabetics, 43% male, 57% female aged 44 to 66 years at baseline. Data from the ARIC food frequency questionnaire at baseline were analyzed to provide GI and GL indices for each subject. Increases of 25 and 30 units for GI and GL respectively were used to describe relationships on incident CHD risk. Adjusted hazard ratios for propensity score with 95% confidence intervals (CI) were used to assess associations. During 17 years of follow-up (1987 to 2004), 1,683 cases of CHD was recorded. Glycemic index was associated with 2.12 fold (95% CI: 1.05, 4.30) increased incident CHD risk for all African Americans and GL was associated with 1.14 fold (95% CI: 1.04, 1.25) increased CHD risk for all whites. In addition, GL was also an important CHD risk factor for white non-diabetics (HR=1.59; 95% CI: 1.33, 1.90). Furthermore, within stratum of BMI 23.0 to 29.9 in non-diabetics, GI was associated with an increased hazard ratio of 11.99 (95% CI: 2.31, 62.18) for CHD in African Americans, and GL was associated with 1.23 fold (1.08, 1.39) increased CHD risk in whites. Body mass index modified the effect of GI and GL on CHD risk in all whites and white non-diabetics. For HTN, both systolic blood pressure and diastolic blood pressure modified the effect on GI and GL on CHD risk in all whites and African Americans, white and African American non-diabetics, and white diabetics. Further studies should examine other factors that could influence the effects of GI and GL on CHD risk, including dietary factors, physical activity, and diet-gene interactions. ^

A review of the published literature on interventions to increase compliance with follow-up outpatient medical appointments in primary care practice

Effective strategies for patient follow-up compliance in family practice are essential for the prevention and early detection of disease with the consequences of decreasing morbidity and mortality. With effective appointment reminder systems in place, physicians can better manage the overall health of their patients by providing preventive care as well. This literature review examines intervention strategies used by the authors, the compliance rate of appointment adherence using these techniques, as well as theories relating to study outcomes. The findings of this study may be used as an educational tool by practices to suggest which intervention strategies might be the most effective for their clinic.^

Evaluation of the association between cryptosporidiosis outbreaks and two interactive water fountain parks: Epidemiologic analysis and implications for public health

Background. A community-wide outbreak of cryptosporidiosis occurred in Dallas County during the summer of 2008. A subset of cases occurring with onset of illness within a 2 week interval was epidemiologically linked to 2 neighborhood interactive water fountain parks. ^ Methods. A case control study was conducted to evaluate risk factors associated with developing illness with cryptosporidiosis from the fountain parks. Cases were selected from a line list from the epidemiological study. The selection for the controls was either healthy family members or a daycare center nearby. Cases and controls were not matched. ^ Results. Interviews were completed for 44 fountain park attendees who met case definition and 54 community controls. Twenty-seven percent (27.3%) of the cases and 13.0% of the controls were between the ages of 0–4 years. Thirty-nine percent (38.6%) of the cases and 24.1% of the controls were between the ages of 5–13 years. Fourteen percent (13.6%) of the cases and 33.3% of the controls were between the ages of 14–31 years. Twenty percent (20.5%) of the cases and 29.6% of the controls were between the ages of 32–63 years. 47.7% of the cases and 42.6% of the controls were males. Fountain park attendees who reported having been splashed in the face with water were 10 times more likely to become ill than controls (OR = 10.0, 95% CI = 2.8–35.1). Persons who reported having swallowed water from the interactive fountains were 34 times more likely to become ill than controls (OR = 34.3, 95%CI = 9.3–125.7). ^ Conclusion. Prompt reporting of cases, identification of outbreak sources, and immediate implementation of remediation measures were critical in curtailing further transmission from these particular sites through the remainder of the season. This investigation underscores the potential for cryptosporidiosis outbreaks to occur in interactive fountain parks, and the need for enhanced preventive measures in these settings. Education of the public regarding avoidance of behaviors such as drinking water from interactive fountains is also an important component of public health prevention efforts. ^

THE RELATIONSHIP BETWEEN DEGREE OF BLOOD PRESSURE REDUCTION AND MORTALITY AMONG HYPERTENSIVES IN THE HYPERTENSION DETECTION AND FOLLOW-UP PROGRAM

The relationship between degree of diastolic blood pressure (DBP) reduction and mortality was examined among hypertensives, ages 30-69, in the Hypertension Detection and Follow-up Program (HDFP). The HDFP was a multi-center community-based trial, which followed 10,940 hypertensive participants for five years. One-year survival was required for inclusion in this investigation since the one-year annual visit was the first occasion where change in blood pressure could be measured on all participants. During the subsequent four years of follow-up on 10,052 participants, 568 deaths occurred. For levels of change in DBP and for categories of variables related to mortality, the crude mortality rate was calculated. Time-dependent life tables were also calculated so as to utilize available blood pressure data over time. In addition, the Cox life table regression model, extended to take into account both time-constant and time-dependent covariates, was used to examine the relationship change in blood pressure over time and mortality.^ The results of the time-dependent life table and time-dependent Cox life table regression analyses supported the existence of a quadratic function which modeled the relationship between DBP reduction and mortality, even after adjusting for other risk factors. The minimum mortality hazard ratio, based on a particular model, occurred at a DBP reduction of 22.6 mm Hg (standard error = 10.6) in the whole population and 8.5 mm Hg (standard error = 4.6) in the baseline DBP stratum 90-104. After this reduction, there was a small increase in the risk of death. There was not evidence of the quadratic function after fitting the same model using systolic blood pressure. Methodologic issues involved in studying a particular degree of blood pressure reduction were considered. The confidence interval around the change corresponding to the minimum hazard ratio was wide and the obtained blood pressure level should not be interpreted as a goal for treatment. Blood pressure reduction was attributed, not only to pharmacologic therapy, but also to regression to the mean, and to other unknown factors unrelated to treatment. Therefore, the surprising results of this study do not provide direct implications for treatment, but strongly suggest replication in other populations. ^

ACCURACY OF THE BRCAPRO RISK ASSESSMENT MODEL IN MALES PRESENTING TO MD ANDERSON FOR BRCA TESTING

ACCURACY OF THE BRCAPRO RISK ASSESSMENT MODEL IN MALES PRESENTING TO MD ANDERSON FOR BRCA TESTING Publication No. _______ Carolyn A. Garby, B.S. Supervisory Professor: Banu Arun, M.D. Hereditary Breast and Ovarian Cancer (HBOC) syndrome is due to mutations in BRCA1 and BRCA2 genes. Women with HBOC have high risks to develop breast and ovarian cancers. Males with HBOC are commonly overlooked because male breast cancer is rare and other male cancer risks such as prostate and pancreatic cancers are relatively low. BRCA genetic testing is indicated for men as it is currently estimated that 4-40% of male breast cancers result from a BRCA1 or BRCA2 mutation (Ottini, 2010) and management recommendations can be made based on genetic test results. Risk assessment models are available to provide the individualized likelihood to have a BRCA mutation. Only one study has been conducted to date to evaluate the accuracy of BRCAPro in males and was based on a cohort of Italian males and utilized an older version of BRCAPro. The objective of this study is to determine if BRCAPro5.1 is a valid risk assessment model for males who present to MD Anderson Cancer Center for BRCA genetic testing. BRCAPro has been previously validated for determining the probability of carrying a BRCA mutation, however has not been further examined particularly in males. The total cohort consisted of 152 males who had undergone BRCA genetic testing. The cohort was stratified by indication for genetic counseling. Indications included having a known familial BRCA mutation, having a personal diagnosis of a BRCA-related cancer, or having a family history suggestive of HBOC. Overall there were 22 (14.47%) BRCA1+ males and 25 (16.45%) BRCA2+ males. Receiver operating characteristic curves were constructed for the cohort overall, for each particular indication, as well as for each cancer subtype. Our findings revealed that the BRCAPro5.1 model had perfect discriminating ability at a threshold of 56.2 for males with breast cancer, however only 2 (4.35%) of 46 were found to have BRCA2 mutations. These results are significantly lower than the high approximation (40%) reported in previous literature. BRCAPro does perform well in certain situations for men. Future investigation of male breast cancer and men at risk for BRCA mutations is necessary to provide a more accurate risk assessment.

Considering Social Factors and Potential Moderation Effects in Children’s Health Research

In light of dramatic changes in American family demography in recent decades, there is a growing recognition that family structure is one of a host of important social factors contributing to children’s health and well-being. The article by Augustine and Kimbro contributes to a growing body of research linking children’s family structure and health outcomes, focusing specifically on the association between family living arrangements and children’s risk of obesity. Their analyses are especially helpful in suggesting that family scholars should pay more attention to potential heterogeneity in relationships between family structure and children’s outcomes.

UNDERSTANDING NURSE CREATED COGNITIVE ARTIFACTS: PERSONALLY-CREATED-COGNITIVE-ARTIFACTS AS EXTERNAL REPRESENTATIONS OF DISTRIBUTED COGNITION

Manuscript 1: “Conceptual Analysis: Externalizing Nursing Knowledge” We use concept analysis to establish that the report tool nurses prepare, carry, reference, amend, and use as a temporary data repository are examples of cognitive artifacts. This tool, integrally woven throughout the work and practice of nurses, is important to cognition and clinical decision-making. Establishing the tool as a cognitive artifact will support new dimensions of study. Such studies can characterize how this report tool supports cognition, internal representation of knowledge and skills, and external representation of knowledge of the nurse. Manuscript 2: “Research Methods: Exploring Cognitive Work” The purpose of this paper is to describe a complex, cross-sectional, multi-method approach to study of personal cognitive artifacts in the clinical environment. The complex data arrays present in these cognitive artifacts warrant the use of multiple methods of data collection. Use of a less robust research design may result in an incomplete understanding of the meaning, value, content, and relationships between personal cognitive artifacts in the clinical environment and the cognitive work of the user. Manuscript 3: “Making the Cognitive Work of Registered Nurses Visible” Purpose: Knowledge representations and structures are created and used by registered nurses to guide patient care. Understanding is limited regarding how these knowledge representations, or cognitive artifacts, contribute to working memory, prioritization, organization, cognition, and decision-making. The purpose of this study was to identify and characterize the role a specific cognitive artifact knowledge representation and structure as it contributed to the cognitive work of the registered nurse. Methods: Data collection was completed, using qualitative research methods, by shadowing and interviewing 25 registered nurses. Data analysis employed triangulation and iterative analytic processes. Results: Nurse cognitive artifacts support recall, data evaluation, decision-making, organization, and prioritization. These cognitive artifacts demonstrated spatial, longitudinal, chronologic, visual, and personal cues to support the cognitive work of nurses. Conclusions: Nurse cognitive artifacts are an important adjunct to the cognitive work of nurses, and directly support patient care. Nurses need to be able to configure their cognitive artifact in ways that are meaningful and support their internal knowledge representations.